1. Field of the Invention
The present invention relates to an RNAi compound and an expression plasmid for inhibiting expression of Thrombospondin-1, a pharmaceutical composition containing the RNAi compound, and a method of treating cancer using the RNAi compound.
2. Description of Related Art
The Thrombospondin protein family consists of thrombospondin 1-5. Thrombospondin-1 (TSP-1) is widely distributed in normal tissue, including heart, lung, liver, spleen and stomach. TSP-1 is mainly secreted by platelets and dendritic cells (DCs), and has multiple biological functions including inhibition of angiogenesis, apoptosis, and activation of transforming growth factor beta (TGF-β) and immune regulation.
Dendritic cells play a major role on activating adoptive immune responses and express TSP-1 during its inactivation. Then, the expressed TSP-1 converts the TGF-β from a latent state into an activated state. The TGF-β is a regulation factor of the immune system, and converts effect T cells into regulatory T cells to suppress immune responses. TSP-1 also interacts with CD47 on T cells to enhance the apoptosis of T cells and the formation of regulatory T cells, and inhibit the immune responses resulting from inflammation. Hence, the immune responses can be improved if the expression of TSP-1 is inhibited.
Conventional immune therapy is accomplished by inducing an immune response with abundant tumor-associated antigens. However, abundant inhibitory cytokines are also generated, which further induce the proliferation of regulatory T cells of patients. The proliferation of regulatory T cells may suppress immune responses. In addition, the tumor-associated antigens are autoantigens, which may cause autoimmune diseases.
In addition, it has been reported that CD25 monoclonal antibodies can be used to suppress regulatory T cells to improve the effect of immune therapy. However, the production cost of monoclonal antibodies is high, and the monoclonal antibodies may cause undesired systematic suppression.
Therefore, it is desirable to provide a drug or an improved method to treat cancer through immune therapy.